A Trial Aiming to Assess the Safety and Activity of the Combination of Cabozantinib Plus Lanreotide in GEP and NET

NCT04427787 | Unknown Phase 2

• 1 other identifier: 2019-004506-10
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase II trial aiming to assess the safety and activity of the combination of cabozantinib plus lanreotide in gastroenteropancreatic (GEP) and thoracic neuroendocrine tumor (NET): The LOLA trial

Conditions

Metastatic Well Differentiated Neuroendocrine Neoplasm; Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  according to RECIST, v1.1 defined as complete response or partial response after treatment administration

  42 months

• Primary Safety Endpoint

  Adverse Events (AE) grade 3-5 according to NCI-CTCAE v5.0 grade

  42 months

Secondary Outcomes (4)

• Progression-free survival (PFS)

  42 months

• Safety Endpoint

  42 months

• Clinical effectiveness endpoint

  42 months

• Exploratory objectives analysis

  42 months

Study Arms (1)

Cabozantinib+lanreotide

EXPERIMENTAL

Cabozantinib will be administered orally at a dose of 60 mg/day continuously in combination with Lanreotide 120 mg injection every 28 days. Both treatments will start the same day

Drug: Cabozantinib; Drug: Lanreotide

Interventions

Cabozantinib DRUG

Cabozantinib will be administered orally at a dose of 60 mg/day

Also known as: Cabometyx

Cabozantinib+lanreotide

Lanreotide DRUG

Lanreotide will be administrated 120 mg injection every 28 days

Also known as: IPSTYL

Cabozantinib+lanreotide

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• voluntary written informed consent obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care;
• Patients with unresectable, advanced or metastatic neuroendocrine well differentiated GEP-NET (pancreatic NET (G2-G3), Small Intestinal NET, stomach NET, rectum NET) with Ki67 10%.
• Patients with unresectable, advanced or metastatic neuroendocrine well differentiated thoracic NET (typical and atypical lung NET, thymus NET)
• Patients with unresectable, advanced or metastatic neuroendocrine well differentiated unknown primary NET with Ki67 10%.
• Locally advanced or metastatic disease documented as progressive by RECIST v1.1. on CT-scan or MRI at baseline and within 12 months prior to baseline.
• disease that is not amenable to surgery with curative intent;
• presence of at least one measurable target lesion for further evaluation according to RECIST v1.1;
• age ≥18 years;
• eastern Cooperative Oncology Group (ECOG) performance status 0 or 1(see APPENDIX I)
• Octreoscan and/or positron emission tomography (PET) 68 Gallium-Dotatoc (68Ga) positive and/or Immuno-histochemistry (IHC) for SSTR2;
• advanced GEP, thoracic and unknown origin NET limited to treatment naïve patients or who have received maximum 1 prior systemic regimen for metastatic disease (biological therapy, chemotherapy or somatostatin analogs, including PRRT);
• Prior PRRT therapy must be completed at least 6 months prior to enrollment;
• Prior treatment with somatostatin analogs, biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, and/or radiation must be completed at least 28 days prior to registration;
• Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective internal radiation therapy) or ablative therapies must be completed at least 28 days prior to registration;
• Prior treatment with cabozantinib or lanreotide are not allowed;

You may not qualify if:

• Patients with undifferentiated, poorly differentiated GEP-NET, Thoracic or unknown primary NET;
• Previous therapy for advanced disease \> 1 line; any medical adjuvant treatment must have been stopped at least six months before entry into the study;
• Prior treatment with dose superior or equal to 120 mg per month of lanreotide;
• Prior treatment with cabozantinib;
• Prior treatment with any other tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors is permitted. Prior treatment with non-VEGF-targeted angiogenic inhibitors such as Everolimus is permitted;
• Patients who stopped Everolimus or tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors treatment less than 4 weeks prior to the start of the study;
• Patients with concomitant treatment with Interferon;
• Patients previously treated with chemotherapy, loco-regional therapy (e.g., chemoembolization) or interferon with last administration less than 4 weeks prior to the start of the study or with toxicity not resolved to less or equal grade 1 at the start of the study;
• diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri;
• history of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA see Appendix II);
• prolongation of QT interval: Cabozantinib should be used with caution in patients with a history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances (e.g., hypokaliemia, family history of long QT Syndrome). Corrected QT interval calculated by the Fridericia formula (QTcF) 500 ms within 28 days before registration should be shown. Only subjects with a baseline QTcF 500 ms are eligible for the study.
• Note: If the QTcF was \> 500 ms in the first ECG, a total of 3 ECGs were to be performed. If the average of these 3 consecutive results for QTcF was ≤ 500 ms, the subject met eligibility in this regard.
• history of aneurysms and arterial dissections. The use of VEGF pathway inhibitors in patients with or without hypertension may favor the formation of aneurysms and / or arterial dissections. Before starting cabozantinib, this risk must be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
• poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90 millimeters of mercury(mmHg)\];
• history of cerebrovascular accidents, including transient ischemic attack (TIA), history of thromboembolic events (including pulmonary embolism) or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible;

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Related Publications (9)

• Caplin ME, Pavel M, Cwikla JB, Phan AT, Raderer M, Sedlackova E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Jul 17;371(3):224-33. doi: 10.1056/NEJMoa1316158.

  PMID: 25014687 RESULT

• Susini C, Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol. 2006 Dec;17(12):1733-42. doi: 10.1093/annonc/mdl105. Epub 2006 Jun 26.

  PMID: 16801334 RESULT

• Krantic S, Goddard I, Saveanu A, Giannetti N, Fombonne J, Cardoso A, Jaquet P, Enjalbert A. Novel modalities of somatostatin actions. Eur J Endocrinol. 2004 Dec;151(6):643-55. doi: 10.1530/eje.0.1510643.

  PMID: 15588232 RESULT

• Chalabi M, Duluc C, Caron P, Vezzosi D, Guillermet-Guibert J, Pyronnet S, Bousquet C. Somatostatin analogs: does pharmacology impact antitumor efficacy? Trends Endocrinol Metab. 2014 Mar;25(3):115-27. doi: 10.1016/j.tem.2013.11.003. Epub 2014 Jan 7.

  PMID: 24405892 RESULT

• Rai U, Thrimawithana TR, Valery C, Young SA. Therapeutic uses of somatostatin and its analogues: Current view and potential applications. Pharmacol Ther. 2015 Aug;152:98-110. doi: 10.1016/j.pharmthera.2015.05.007. Epub 2015 May 5.

  PMID: 25956467 RESULT

• Pola S, Cattaneo MG, Vicentini LM. Anti-migratory and anti-invasive effect of somatostatin in human neuroblastoma cells: involvement of Rac and MAP kinase activity. J Biol Chem. 2003 Oct 17;278(42):40601-6. doi: 10.1074/jbc.M306510200. Epub 2003 Aug 5.

  PMID: 12902325 RESULT

• Azar R, Najib S, Lahlou H, Susini C, Pyronnet S. Phosphatidylinositol 3-kinase-dependent transcriptional silencing of the translational repressor 4E-BP1. Cell Mol Life Sci. 2008 Oct;65(19):3110-7. doi: 10.1007/s00018-008-8418-2.

  PMID: 18810319 RESULT

• Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Horsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):501-13. doi: 10.1056/NEJMoa1003825.

  PMID: 21306237 RESULT

• Corti F, Brizzi MP, Amoroso V, Giuffrida D, Panzuto F, Campana D, Prinzi N, Milione M, Cascella T, Spreafico C, Randon G, Oldani S, Leporati R, Scotto G, Pulice I, Stocchetti BL, Porcu L, Coppa J, Di Bartolomeo M, de Braud F, Pusceddu S. Assessing the safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic and thoracic neuroendocrine tumors: rationale and protocol of the phase II LOLA trial. BMC Cancer. 2023 Sep 26;23(1):908. doi: 10.1186/s12885-023-11287-2.

  PMID: 37752423 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

cabozantinib; lanreotide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Sara Pusceddu, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara Pusceddu, MD

CONTACT

+390223903066; sara.pusceddu@istitutotumori.mi.it

Lavinia Biamonte, Dr.ssa

CONTACT

+390223903030; lavinia.biamonte@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 11, 2020
• Study Start: June 20, 2020
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2023
• Last Updated: September 5, 2021

Record last verified: 2021-09

Locations

IT (1)